This application relates to topical compositions containing additional N-acetylamino acids and related N-acetyl compounds, and their use in alleviating or improving various cosmetic conditions and dermatological disorders.
In PCT Application No. PCT/US96/16534, filed Oct. 16, 1996, entitled xe2x80x9cTopical Compositions Containing N-Acetylcysteine and Odor Masking Materials,xe2x80x9d topical compositions comprising from 0.01% to 50% of N-acetylcysteine or a derivative of N-acetylcysteine, from 0.01% to 0.5% of an odor masking material, and a topical carrier are disclosed to improve the appearance of skin.
N-Acetylcysteine is N-acetylated cysteine which is a thiol containing amino acid, also called xcex1-acetamido-xcex2-mercaptopropanoic acid. Topical compositions containing N-acetylcysteine have been claimed to improve physical appearance of the skin including cosmetic wrinkles. N-acetylcysteine contains a free thiol group, thus, is known as an antioxidant. The affect of N-acetylcysteine is claimed to be due to its antioxidant property. N-Acetylcysteine, as an antioxidant substance, also has been indicated as protective against pulmonary oxygen toxicity (Eur. Respir. J. 2: 116-126 (1989)).
N-acetylcysteine, however, is also associated with a number of significant drawbacks. N-acetylcysteine is known to degrade under ordinary storage conditions and result in a malodorous smell. The malodor is suggested to be caused by the release of thiol compounds and hydrogen sulfide upon degradation. Thus, topical compositions containing N-acetylcysteine have little or no commercial use due to the strong malodor of N-acetylcysteine.
PCT/US96/16534 claimed that the malodor could be masked by addition of certain perfume chemicals at concentrations ranging from 0.01 to 0.5% by weight. The perfume chemicals include aromatic esters, aliphatic esters, aromatic alcohol, aliphatic alcohols, aliphatic ketones, aromatic aldehydes, aliphatic aldehydes, aromatic ethers and aliphatic ethers. Because the malodorous thiol compounds and hydrogen sulfide have not been chemically neutralized or destroyed, however, the transient masking effect is not a satisfactory solution for most consumers, and therefore is not a viable approach for commercialization of N-acetylcysteine in the cosmetic industry.
Our U.S. Pat. Nos. 6,159,485 and 6,524,593 disclose and claim N-acetyl aldosamines, N-acetylated amino acids and related compounds which are topically effective for various cosmetic conditions and dermatological indications including the signs of skin, nail and hair changes associated with intrinsic and/or extrinsic aging. The N-acetylated amino acids and related compounds do not necessarily contain thiol groups and are not necessarily antioxidants.
It is an object of this invention to provide additional methods and compositions which can alleviate various cosmetic conditions and dermatological disorders including the signs of skin, nail and hair changes associated with intrinsic and/or extrinsic aging and extrinsic factors, and other skin conditions associated with or due to itching and/or inflammation, including pruritus.
We have now discovered additional N-acetylamino acids and related N-acetyl compounds which have unexpected properties. Topical applications of compositions comprising N-acetylamino acids and related N-acetyl compounds have been found to improve cosmetic conditions and dermatological disorders including cosmetic as well as clinical signs of changes in skin, nails and hair associated with intrinsic and/or extrinsic aging, or the damages caused by extrinsic factors such as sunlight, radiation, air pollution, wind, cold, dampness, heat, chemicals, smoke, cigarette smoking, and various oxidants.
The signs of skin changes associated with intrinsic and/or extrinsic aging and the skin damages caused by extrinsic factors include thinning of skin; fragile skin; deepening of skin lines and fine lines; wrinkles, including fine and course wrinkles; blemishes; atrophy; pigmented spots, blotches and mottles, nodules and mottled skin; pre-cancerous lesions; elastotic changes characterized by leathery, lusterless, uneven, coarse, rough, dry and/or yellowish skin; loss of skin elasticity and recoilability; loss of skin lubricating substances; changes in qualities and quantities of glycosaminoglycans and proteoglycans and collagen and elastic fibers; solar elastosis; decrease in collagen fibers; diminution in the number and diameter of elasitic fibers in the papillary dermis; atrophy; stretch marks; reduction in subcutaneous adipose tissue; deposition of abnormal elastic materials in the dermis leading to thickening of the dermis; older-looking skin; and telangiectatic skin.
The signs of nails and hair changes associated with intrinsic aging and the damages caused by extrinsic factors include thinning, fragility, splitting, lack of luster, uneven surface, and loss of flexibility and elasticity.
In accordance with the objects of the invention, compositions comprising at least one compound selected from the group consisting of certain N-acetylamino acids and related N-acetyl compounds, present in a therapeutically effective amount and in a pharmaceutically acceptable vehicle for topical treatment of cosmetic conditions or dermatological disorders are provided. In one embodiment of the invention, the compositions further comprise a cosmetic, pharmaceutical, or other topical agent.
Also in accordance with the objects of the invention, a method for treating cosmetic conditions and dermatological disorders comprising topically applying a therapeutically effective amount of a composition comprising at least one compound selected from the group consisting of certain N-acetylamino acids and related N-acetyl compounds, in a pharmaceutically acceptable vehicle is provided. In one embodiment of the invention, the method comprises topically applying a therapeutically effective amount of a composition comprising at least one compound selected from the group consisting of certain N-acetylamino acids and related N-acetyl compounds, and at least one cosmetic, pharmaceutical, or other topical agent, in a pharmaceutically acceptable vehicle.
The additional N-acetylamino acids and related N-acetyl compounds which are useful for topical treatment of skin, nail and hair changes associated with intrinsic and/or extrinsic aging and extrinsic factors include, inter alia, N-acetylamino acids selected from N-acetyl pyroglutamic acid, N-acetyl-phenylalaninol, N,S-diacetylamino acids, and isomeric or nonisomeric, free acid, salt, lactone, amide, or ester forms thereof; and related N-acetyl compounds selected from N-acetylpolyamines, N,Nxe2x80x2-diacetylpolyamines, N-acetyl-caldine, N-acetyl-spermidine, N-acetyl-homospermidine, N-acetyl-thermine, N-acetyl-spermine, N-acetyl-thermospermine, N-acetyl-homospermine, N-acetyl-caldopentamine, N-acetyl-homocaldopentamine, N-acetyl-caldohexamine, N-acetyl-homocaldohexamine, N-acetyl-tris(3-aminopropyl)amine, N-acetyl-tetrakis(3-aminopropyl)amine, N-acetyl-amantadine, N-acetyl-adenosine, N-acetyl-adenosine-phosphoric acid, N-acetyl-piperazine, and N-acetyl guanine.
Additional objects and advantages of the invention will be set forth in part in the description that follows, and in part will be obvious from the description, or may be learned by practice of the invention. The objects and the advantages of this invention may be realized and obtained by means of the compositions and methods particularly pointed out in the appended claims.